Moores Cancer Center. Courtesy UC San Diego Health

A multi-institutional team of researchers, including some from UC San Diego, has identified both the genetic abnormalities that drive pre-cancer cells into becoming an invasive type of head and neck cancer and patients who are least likely to respond to immunotherapy, it was announced Monday.

“Through a series of surprises, we followed clues that focused more and more tightly on specific genetic imbalances and their role in the effects of specific immune components in tumor development,” said co-principal investigator Webster Cavenee, a professor emeritus at UCSD School of Medicine.

“The genetic abnormalities we identified drive changes in the immune cell composition of the tumors that, in turn, dictates responsiveness to standard of care immune checkpoint inhibitors.”

In Monday’s online issue of the Proceedings of the National Academy of Sciences, the researchers describe the role of somatic copy-number alterations — abnormalities that result in the loss or gain in a copy of a gene — and the loss of chromosome 9p in the development of human papillomavirus-negative head and neck cancer.

The loss of chromosome 9p and the deletion two neighboring genes found on chromosome 9p was associated with resistance to immune checkpoint inhibitors, a type of cancer immunotherapy that uses antibodies to make tumor cells visible to a patient’s immune system.

“Although programmed death-1 immune checkpoint inhibitors represent a major breakthrough in cancer treatment, only 15% of patients with HPV- negative head and neck cancer respond to treatment,” said co-principal investigator Dr. Scott M. Lippman, senior associate dean, associate vice chancellor for cancer research and care and Chugai Pharmaceutical Chair in Cancer at the UCSD School of Medicine.

“The ability to predict a patient’s response or resistance to this class of therapies, a major unmet clinical need, is a unique and novel discovery,” he said. “Knowing who will not respond avoids losing several months to ineffective therapy with huge financial costs and impacts to quality of life.”

Lippman is director of UCSD’s Moores Cancer Center and a medical oncologist who specializes in the treatment of patients with head and neck cancer at UCSD Health.

The National Cancer Institute estimates about 54,000 new head and neck cancer cases will be diagnosed in the United States this year, with 10,850 deaths. HPV-negative head squamous cell carcinomas are the most common, increasing and lethal subtype of this malignancy worldwide, Lippman said.

“The data serves as a powerful predictive marker, transforming standard of care for precision immunotherapy for patients with advanced, recurrent head and neck cancer,” Lippman said. “And, while we focused in an unprecedented extensive interrogation of the most globally lethal form of head and neck squamous cancer, accounting for more than 300,000 deaths annually, the application may be useful in a wide variety of solid tumors for which immune checkpoint inhibitors comprises standard of care.”

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